Forum for Science, Industry and Business

New immune cell found to be a key to inflammatory diseases

04.10.2005

The molecular roots of inflammatory and autoimmune diseases such as asthma, arthritis, and multiple sclerosis (MS) have been discovered by a team of researchers led by The University of Texas M. D. Anderson Cancer Center. They say their findings may point to ways to effectively treat these diseases - if not stop them before they start.

In a lead article in the November issue of Nature Immunology (released online on Oct. 2), the scientists report finding a novel type of "T helper" cell they say is the culprit for initiating chronic inflammation and autoimmunity in a variety of body tissues. This newly described T cell - which they call inflammatory TH cells (or THi) - produces interleukin 17 (IL-17), a potent cytokine that researchers have already linked to an immune system gone awry.

"We suspected that IL-17 is a player in autoimmune and inflammatory diseases, but we didnt understand where IL-17 came from before this finding," says the studys lead investigator, Chen Dong, Ph.D., an associate professor in the Department of Immunology.

"Now we have discovered the source of IL-17 and also have solidly demonstrated that these are the crucial cells that regulate tissue inflammation in autoimmune disease and asthma," he says. "These findings suggest that shutting down the activity of these THi cells might stop chronic inflammatory diseases from developing in the first place."

He adds that while such drugs are years away from development and clinical trials, agents that block IL-17 could represent an effective treatment, based on these results.

Dong and four other M. D. Anderson researchers collaborated with scientists from the University of Washington, the Institute for Systems Biology in Seattle and Johns Hopkins School of Medicine.

While the findings have no immediate relevance to the field of oncology, it is known that cancer can arise from inflammatory processes. Further understanding of how the immune system functions, and how it can go awry, is important, Dong says.

T cells are white blood cells that play a variety of roles in the immune system, including the identification of foreign molecules in the body, such as bacteria and viruses, and the activation and deactivation of other immune cells.

T helper cells are specific T cells that have receptors that recognize and bind to fragments (known as antigens) of the invaders that already have been displayed on the surface of other immune system cells. (These T helper cells are also called CD4 T cells since they express CD4 molecules.) Once the antigen has been bound, these T helper cells become activated, and they morph into "effector" cells which then boost an immune response by secreting "cytokine" molecules such as interleukins and interferons.

Before this study, two such different types of effector T helper cells had been known - type I (TH1), linked to the bodys response to microbial infection, and type 2 (TH2), which plays a crucial function in production of B cell antibodies and also is associated with development of allergies.

Although TH1 and TH2 are known to produce powerful cytokines - such as interferon-gamma (IFN-g) and allergy-associated interleukin 4 (IL-4), respectively - they are not inflammatory or associated with production of IL-17, which sets off an errant immune response that results in tissue inflammation.

Researchers could not understand the origins of such an inflammatory response in body tissues. The only clue they had was that excess IL-17 molecules are found in arthritic joints, in lungs swollen by asthma and in brain cells that lead to nerve degeneration and the onset of MS. "But we didnt know which T cells were responsible for secreting IL-17," Dong says. To find out where IL-17 came from, the researchers designed a series of cell culture studies and mouse experiments. In brief, they "educated" T helper cells to become IL-17 producing cells. They found that IL-17 is triggered by a unique set of signals that now define this new "lineage" of T helper cells. "They are completely different from TH1 and TH2 effector cells," says Dong. They then used a mouse model of MS and demonstrated that they could stop development of the disease with an antibody agent that blocked IL-17. Finally, they developed a transgenic mouse model of asthma and found that, by producing excessive IL-17 in the lung, they were able to produce asthmalike symptoms.

Dong says the researchers hypothesize that these newly discovered THi cells travel to selected body tissues and release IL-17. This action, in turn, stimulates expression of "chemokines," which results in a rush of inflammatory cells into the tissue. Thus a chronic inflammatory reaction is set up, he says.

The scientists dont know what initially sets off activation of the newly discovered T helper cell in diseases such as arthritis and asthma, Dong says. "We dont know why these dangerous helper T cells are activated in the patients, but we now know how they function, and that should take us a long way to understanding and treating these and other inflammatory and autoimmune diseases."

Die letzten 5 Focus-News des innovations-reports im Überblick:

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...